Pathways to Discovery: Spring 2012

KISS1 is an interesting protein that seems to at least play a role in determining which subset of patients develop brain metastases from breast cancer.
—Maciej Lesniak, MD

The most common cause of death from breast cancer is not the primary tumor, but from subsequent tumors, such as those that spread to the brain. One in five women with metastatic breast cancer will contract a brain lesion, and median survival for those patients is less than a year after diagnosis, according to the American Cancer Society.

Yet physicians currently have few tests to predict which breast tumors will eventually
spread to the brain and which will not. Because no two patients' cancers are alike, physicians recognize that they need reliable biomarkers to help predict how the disease will progress and guide treatment decisions.

Maciej Lesniak, MD, professor of surgery and neurology and director of neurological oncology, often treats patients whose breast cancer has spread to the brain. "Are there any risk factors or biological phenomena behind this form of the disease?" Dr. Lesniak asked. "That was the question that we set out to answer."

Treating cancer involves a collaborative effort, as does finding predictive cancer
biomarkers. The ongoing search for factors that can help physicians calculate the risk of brain metastasis in breast cancer patients has united researchers from multiple disciplines—neurosurgery, oncology, pathology, and health studies—and multiple institutions—UChicago, University of Alabama at Birmingham, and Kansas Medical Center.

The first product of this large collaboration was the discovery of a promising biomarker with an innocuous name—KISS1—which was previously associated with the progression of bladder, ovarian, and other cancers. The finding was published late last year in the journal Cancer.

KISS1 Associated with Reduced Metastatic Risk
Using tissue samples from the UCCCC's Specialized Program of Research Excellence (SPORE) in Breast Cancer, the research team, led by Ilya Ulasov, DVM, PhD, a research associate at UChicago, measured KISS1 levels in cancerous breast tissue, non-cancerous breast tissue, and brain lesions from metastatic cancer patients.

The comparison found lower levels of KISS1 protein in the brain metastases relative to breast tumors, suggesting that a reduction of this protein may be associated with increased spread of cancer to the brain. Another analysis found that patients with higher levels of KISS1 expression exhibited slower disease progression
and a reduced chance of developing brain metastases.

"KISS1 is an interesting protein that seems to at least play a role in determining which subset of patients develop brain metastases from breast cancer," said Dr. Lesniak, senior author of the Cancer study.

More Research Necessary
However promising the data, the researchers cautioned that their study is only the first step toward establishing KISS1 as a valid biomarker for predicting the course of
metastatic breast cancer. But if a mechanism is discovered, Dr. Lesniak speculated that KISS1 may hold clues for slowing or preventing brain metastases.

"The question is 'How can you modulate KISS1 expression for the benefit of patients?'" Dr. Lesniak asked. "One approach would be to restore KISS1 expression
in patients with advanced metastatic breast cancer and see whether it makes the tumor less aggressive or less prone to metastatic disease. It's an interesting
thought, but it's probably too premature to know whether that would hold true."